Scenario planning for the Edinburgh city region

This paper examines the application of scenario planning techniques to the detailed and daunting challenge of city re-positioning when policy makers are faced with a heavy history and a complex future context. It reviews a process of scenario planning undertaken in the Edinburgh city region, exploring the scenario process and its contribution to strategies and policies for city repositioning. Strongly rooted in the recent literature on urban and regional economic development, the text outlines how key individuals and organisations involved in the process participated in far-reaching analyses of the possible future worlds in which the Edinburgh city region might find itself

Correlation of immune phenotype with IDH mutation in diffuse glioma.

Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database. TIL and PD-L1 expression were observed in approximately half of WHO grade II/III gliomas. IDH-wt status was associated with significantly higher TIL infiltration and PD-L1 expression among all (grades II-IV) cases (n = 174, P < 0.001) and within the cohort of glioblastomas (n = 131, P < 0.001). In low-grade glioma (LGG) and glioblastoma cohorts of TCGA, significantly higher PD-L1 gene expression levels were evident in IDH-wt compared with IDH-mut samples (LGG: N = 516; P = 1.933e-11, GBM: N = 161; P < 0.009). Lower PD-L1 gene expression was associated with increased promoter methylation (Spearman correlation coefficient -0.36; P < 0.01) in the LGG cohort of TCGA. IDH-mut gliomas had higher PD-L1 gene promoter methylation levels than IDH-wt gliomas (P < 0.01). The immunological tumor microenvironment of diffuse gliomas differs in association with IDH mutation status. IDH-wt gliomas display a more prominent TIL infiltration and higher PD-L1 expression than IDH-mut cases. Mechanistically this may be at least in part due to differential PD-L1 gene promoter methylation levels. Our findings may be relevant for immune modulatory treatment strategies in glioma patients

To know or not to know:should crimes regarding photographs of their child sexual abuse be disclosed to now-adult, unknowing victims?

This paper considers the unexplored question of whether unaware crime victims have rights or interests in knowing and not knowing information pertaining to the crime(s) committed against them. Our specific focus is on whether crimes regarding abusive images (AI) should be disclosed to now-adult victims of child sexual abuse who feature in them. Because these issues have not been addressed in the victimology or criminological literature, we utilise literature in another discipline - health care ethics and law - to inform our analysis. Through engaging with the debate on the right to know and not to know information concerning one’s genetic status, we develop a conceptualisation of the issues regarding unknowing AI victims. A rights-based conceptualisation proves to be largely inappropriate; we contend that, instead, it would be more productive to look to unknowing AI victims’ interests. We argue that the interests at stake are grounded in autonomy and/or spatial privacy, and that in order to find a way to resolve the disclosure dilemma, these interests must be considered alongside consequentialist concerns; disclosing information regarding AI could empower now-adult victims but could well cause them (further) harm. Finally, we consider the implications of our analysis for victimology

Human Pentraxin 3 Binds to the Complement Regulator C4b-Binding Protein

The long pentraxin 3 (PTX3) is a soluble recognition molecule with multiple functions including innate immune defense against certain microbes and the clearance of apoptotic cells. PTX3 interacts with recognition molecules of the classical and lectin complement pathways and thus initiates complement activation. In addition, binding of PTX3 to the alternative complement pathway regulator factor H was shown. Here, we show that PTX3 binds to the classical and lectin pathway regulator C4b-binding protein (C4BP). A PTX3-binding site was identified within short consensus repeats 1–3 of the C4BP α-chain. PTX3 did not interfere with the cofactor activity of C4BP in the fluid phase and C4BP maintained its complement regulatory activity when bound to PTX3 on surfaces. While C4BP and factor H did not compete for PTX3 binding, the interaction of C4BP with PTX3 was inhibited by C1q and by L-ficolin. PTX3 bound to human fibroblast- and endothelial cell-derived extracellular matrices and recruited functionally active C4BP to these surfaces. Whereas PTX3 enhanced the activation of the classical/lectin pathway and caused enhanced C3 deposition on extracellular matrix, deposition of terminal pathway components and the generation of the inflammatory mediator C5a were not increased. Furthermore, PTX3 enhanced the binding of C4BP to late apoptotic cells, which resulted in an increased rate of inactivation of cell surface bound C4b and a reduction in the deposition of C5b-9. Thus, in addition to complement activators, PTX3 interacts with complement inhibitors including C4BP. This balanced interaction on extracellular matrix and on apoptotic cells may prevent excessive local complement activation that would otherwise lead to inflammation and host tissue damage